During the past year we have found that Uteroglobin (UG) is a potent inhibitor of aggregation of both rabbit and human platelets. This is a significant finding since pregnancy induces production of thromboxame A2, a potent mediator of platelet aggregation in the uterus and in the lung. It is possible that UG may counteract the hypercoagulable state of pregnancy. Preliminary data suggest that uteroglobin by its anti-platelet aggregation effects may prevent thrombosis in the microvasulature of the placenta, the uterus and of the lung. Using a sensitive radioimmunoassay, SDS-PAGE and isoelectric focusing we have discovered that a protein similar in molecular weight, PE and immunological crossreactivity to uteroglobin is present in the neonatal human lung. This is the first time the presence of a human counterpart of rabbit uteroglobin has been clearly documented. Experiments underway will delineate the distribution of this protein in different human tissues and its possible function. Furthermore, the exact mechanism of inhibition of platelet aggregation by this protein will be studied in more detail. In addition to the above findings, we have now established several rabbit alveolar and endometrial epithelial cell lines transformed by a temperature sensitive mutant of SV40. These cell lines express both cytoplasmic and nuclear receptors for estradiol and progesterone. When stimulated with progesterone at 40 C the endometrial cells secrete uteroglobin in the medium. Thus, these cells, when fully characterized, will provide an unique tool to (i) determine the biological activity of various progestogenic agents in vitro which is unavailable at present and (ii) study the regulation of expression of the uteroglobin gene in response to progesterone by c-DNA probe analysis.